Prevention of Cardiac Dysfunction During Breast Cancer Therapy (PRADAII)
Breast Cancer Female, Heart Failure
About this trial
This is an interventional prevention trial for Breast Cancer Female focused on measuring LCZ696, CMR, Echocardiography, Cardio-oncology, Circulating biomarkers, Breast Cancer, Anthracyclines
Eligibility Criteria
Inclusion Criteria:
- Women with histological evidence of invasive early breast cancer scheduled for adjuvant therapy with anti-cancer regimens that include anthracyclines
- Eastern Cooperative Oncology Group performance status 0-1
- Sinus rhythm
Exclusion criteria:
- Age <18 years
- Renal failure, i.e. serum creatinine greater than 133 mol/L (1.5mg/dL) or estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73m2
- Hyperkalemia, i.e. serum potassium greater than 5.0 mmol/L
- Systolic blood pressure < 100 mgHg
- Uncontrolled hypertension
- Acute myocardial infarction within the last three months
- Contraindication to ACEI or ARB or sacubitril/valsartan, including previous hypersensitivity reaction, angioedema and renal artery stenosis
- ACEI, ARB, aldosterone antagonist or sacubitril/valsartan use within 4 weeks of study start
- Clear indication for ACEI, ARB, aldosterone antagonist or sacubitril/valsartan therapy, including symptomatic heart failure
- History of hemodynamically significant valvular disease
- Active liver disease, i.e. alanine aminotransferase or aspartate aminotransferase greater than 1.5 times the upper limit of normal
- Participation in another pharmaceutical clinical trial of an investigational medicinal product (IMP) less than 4 weeks prior to inclusion or use of other investigational drugs within 5 halflives of enrollment, whichever is longer
- Conditions that would affect the participants to comply with the study protocol as psychiatric or mental disorders, alcohol abuse or other substance abuse, suspected poor drug compliance, language barriers or other factors
- Contraindication or inability to undergo CMR examination
- Fertile women with inadequate birth control, pregnancy, and/or breastfeeding. Adequate contraception includes oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device or system, vasectomized partner or sexual abstinence. Fertile women are defined as following menarche and until becoming postmenopausal unless permanently sterile. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause
- Life expectancy < 12 months
Sites / Locations
- Akershus University Hospital
- Stavanger University Hospital
- University of North Norway
- St Olavs Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Placebo Comparator
Sacubitril/valsartan
Placebo
Sacubitril/valsartan (target dose 97/103 mg b.i.d.) and matching placebo will be provided orally in a 1:1 parallel fashion stratified by study site and for planned treatment with trastuzumab. Dose titration will be performed as follows: Sacubitril/valsartan 24/26 mg b.i.d. will be administered for 2-4 weeks and provided blood pressure > 100 mmHg, no symptoms of hypotension or other side effects or adverse events (AE), followed by sacubitril/valsartan 49/51 mg b.i.d. for 2-4 weeks. Provided blood pressure > 100 mmHg, no symptoms of hypotension or other side effects or AE a further uptitration to sacubitril/valsartan 97/103 mg b.i.d. will be performed.
Matched to the comparator.